Hamburg, Sarah; (2018) Resting-state EEG in adults with Down syndrome. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Individuals with Down syndrome (DS) show a high degree of inter-subject variability in cognitive ability. Elucidating factors associated with variability in cognitive function can inform us about intellectual disability severity and potentially provide biomarkers of ability for clinical trials targeting cognition in individuals with DS (including trials aimed at preventing cognitive decline). Resting-state electroencephalography (EEG) can be used to obtain information about neural factors that may be underlying variability in cognitive function. This thesis uses eyes-open (EO; n=48) and eyes-closed (EC; n=36) resting-state EEG paradigms in adults with DS free from detectable signs of cognitive decline or dementia to identify EEG measures associated with general cognitive ability, and to investigate age-related changes in EEG activity in this population. Oscillations of interest were then modelled using dynamic causal modelling (DCM) to identify potential neurophysiological mechanisms underlying individual differences in general cognitive ability. Initial analysis suggested that individuals with DS have an overall slower EC EEG spectrum (and particularly strong differences in alpha activity) compared to typically-developing age-matched control subjects (open source control dataset used). Within individuals with DS, increasing age was associated with EEG changes in both paradigms. When controlling for age, higher general cognitive ability was associated with higher delta power (EO only), higher theta power (EC only), and higher alpha peak amplitude (EC only). Modelling the theta-alpha network identified “intrinsic self-inhibition” as the most important neurophysiological parameter underlying the relationship between theta-alpha activity and general cognitive ability in this sample. Further analysis revealed a strong inverse relationship between occipital intrinsic self-inhibition and general cognitive ability. Findings of this thesis enhance our understanding of neural factors associated with individual differences in general cognitive ability in adults with DS, provide a potential biomarker of ability for clinical trials, and indicate potential targets for cognitive enhancement in this population. The finding that increased inhibition may be associated with cognitive impairment in this population is in keeping with animal model literature and warrants further investigation.

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